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Yanpo Si,1,2 Chengcheng Hui,1 Tao Guo,1,2 Mengqi Liu,1 Xiaohui Chen,3 Chunhong Dong,3,4 Shuying Feng5 1Department of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 2Henan Engineering Research Center of Medicinal and Edible Chinese Medicine, Zhengzhou, People’s Republic of China; 3Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of China; 4Henan Key Laboratory of Chinese Medicine for Polysaccharides and Drugs Research, Zhengzhou, People’s Republic of China; 5Medical College, Henan University of Chinese Medicine, Zhengzhou, People’s Republic of ChinaCorrespondence: Tao Guo; Shuying Feng, Henan University of Chinese Medicine, No. 156 JinshuiEast Road, Zhengzhou, 450046, People’s Republic of China, Tel +86 371 65962746 ; +86 371 65934070, Email gt010010@hactcm.edu.cn; fsy@hactcm.edu.cnPurpose: To reveal the potential mechanism of PDA on hepatocellular carcinoma SMMC-7721 cells in vitro.Methods: The cytotoxic activity, colony formation, cell cycle distribution, apoptosis and their associated protein analysis, intracellular reactive oxygen species (ROS) and Ca2+ levels, proteins in Nrf2 and Ntoch pathways and metabolite profiles of PDA against hepatocellular carcinoma were investigated.Results: PDA with cytotoxic activity inhibited cell proliferation and migration, increased intracellular ROS, Ca2+ levels and MCUR1 protein expression in a dose-dependent manner, caused cell cycle arrest in the S phase and induced apoptosis via adjusting the levels of Bcl-2, Bax, and Caspase 3 proteins, and inhibited the activation of Notch1, Jagged, Hes1, Nrf2 and HO-1 proteins. Metabonomics data showed that PDA significantly regulated 144 metabolite levels tend to be normal level, especially carnitine derivatives, bile acid metabolites associated with hepatocellular carcinoma, and mainly enriched in ABC transporter, arginine and proline metabolism, primary bile acid biosynthesis, Notch signaling pathway, etc, and proved that PDA markedly adjusted Notch signaling pathway.Conclusion: PDA exhibited the proliferation inhibition of SMMC-7721 cells by inhibiting ROS/Nrf2/Notch signaling pathway and significantly affected the metabolic profile, suggesting PDA could be a potential therapeutic agent for patients with hepatocellular carcinoma.Keywords: isoquinoline alkaloid, apoptosis, acylcarnitine, bile acids, metabolomics

Xingming Xie,1,2 Chaochun Chen,1,2 Shu Feng,1,3 Shi Zuo,2 Xueke Zhao,3 Haiyang Li1,2 1School of Clinical Medicine, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 3Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, People’s Republic of ChinaCorrespondence: Haiyang LiDepartment of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, 28 Guiyi Street, Guiyang, Guizhou, People’s Republic of ChinaTel/Fax +86 851-6855119Email lihaiyang@gmc.edu.cnPurpose: Acyl-CoA thioesterase 7(ACOT7) plays an important role in the metabolism of fatty acids. Hepatocellular carcinoma (HCC) has an abnormal lipid profile, and the role of ACOT7 in hepatocellular carcinoma has not been detailedly elucidated. Therefore, we conducted the study to explore the role of ACOT7 in HCC.Materials and Methods: The ACOT7 and Krüppel-like factor 13 (KLF13) mRNA expression levels were obtained from The Cancer Genome Atlas (TCGA) database. Bioinformatics analysis identified the underlying upstream regulator of ACOT7. Quantitative real-time PCR was used to detect the expression of mRNA, and immunohistochemical staining and Western blotting were used to detect the expression of protein. Cell Counting Kit-8 and EdU assays were employed to assess the proliferation of HCC cells. Wound-healing and Transwell migration assays were utilized to test the migration ability of HCC cells. Dual-luciferase reporter assay and ChIP assay were used to explore the potential mechanism. Gas chromatography-mass spectrometer was used to analyze the content of free fatty acids. Xenograft tumour growth was used to evaluate the effect of ACOT7 in vivo.Results: According to The Cancer Genome Atlas (TCGA) database, ACOT7 mRNA was found to be upregulated and predicted the poor prognosis. Overexpression of ACOT7 enhanced the proliferation, migration and invasion abilities of HCC cells in vitro, as well as the HCC cells proliferation in vivo. Moreover, ACOT7 overexpression increased the yield of the monounsaturated fatty acid Oleic acid (C18:1), which strengthened the proliferation and migration abilities of HCC cells. Mechanistically, KLF13 transcriptionally promoted ACOT7 expression. Further, KLF13 was also overexpressed in HCC tissues and facilitated HCC progression.Conclusion: Acyl-CoA thioesterase 7 is transcriptionally activated by Krüppel-like factor 13 and promotes the progression of hepatocellular carcinoma.Keywords: acyl-CoA thioesterase 7, Krüppel-like factor 13, hepatocellular carcinoma, unsaturated fatty acid, prognosis

Xiaoning Cen,1,&ast; Yunmei Huang,2,&ast; Zhuangnian Lu,3,&ast; Wenjun Shao,4 Chenyi Zhuo,1 Chongchan Bao,5 Shi Feng,5 Cheng Wei,5 Xiqiang Tang,5 Lijun Cen,5 Wenwen Guo,5 Xinru Tian,5 Qianli Tang,5 Xusen Huang1 1General Surgery, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China; 2Department of Pathology, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China; 3Department of Pediatrics, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China; 4Medical college of Soochow University, Suzhou, Jiangsu, 215000, People’s Republic of China; 5YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qianli TangYouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of ChinaEmail htmgx@163.comXusen HuangGeneral Surgery, Affiliated Hospital of YouJiang Medical University for Nationalities, Baise, 533000, Guangxi, People’s Republic of ChinaEmail hxsfy@163.comBackground: LncRNAs play an important role in tumor initiation and development. However, the underlying involvement of lncRNA expression in colorectal carcinoma remains to be clarified.Methods: All analyses were performed in R software v4.0, SPSS v13.0, and GraphPad Prism 8. The “limma” package was used to identify differentially expressed lncRNAs between two groups with the threshold of |logFC| > 1 and P < 0.05. The “Survival” package was used to conduct survival analysis. HCT8 and SE480 cell lines were used to conduct further phenotype experiments, including transwell, wound-healing, CCK8 and colony formation assay. Gene set enrichment analysis was used to explore the biological pathway difference in high and low IGFL2-AS1 patients.Results: The lncRNA IGFL2-AS1 was highly expressed in colon adenocarcinoma (COAD) tissue and cell lines (HCT116, HCT8, HCT129, and SW480). The COAD patients with high IGFL2-AS1 were associated with a worse prognosis. Meanwhile, the knockdown of IGFL2-AS1 could significantly suppress the proliferation and invasion of COAD cells. Gene set enrichment analysis showed that the top five biological pathways involving IGFL2-AS1 were angiogenesis, epithelial–mesenchymal transition, KRAS signaling, myogenesis, and coagulation. Western blot results showed that the inhibition of IGFL2-AS1 could significantly reduce the N-cadherin, HIF1A and KRAS protein expression, yet increase the E-cadherin protein level. IGFL2-AS1 was also positively correlated with M0 macrophages, M2 macrophages, and neutrophils but negatively correlated with CD4+ memory T cells and CD8+ T cells.Conclusion: IGFL1-AS1 could seriously worsen patient outcomes and facilitate COAD progression, thus serving as an independent tumor marker.Keywords: IGFL2-AS1, lncRNA, colon cancer, immune

Yanxiang Shao,1,&ast; Thongher Lia,1,&ast; Yaohui Wang,1,&ast; Kan Wu,1 Xu Hu,1 Yang Liu,1 Shuyang Feng,1 Shangqing Ren,1,2 Zhen Yang,1,3 Sanchao Xiong,1 Weixiao Yang,1 Qiang Wei,1 Hao Zeng,1 Xiang Li1 1Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Robotic Minimally Invasive Surgery Center, Sichuan Academy of Medical Sciences & Sichuan Provincial People’s Hospital, Chengdu, 610072, People’s Republic of China; 3Department of Urology, Chengdu Second People’s Hospital, Chengdu, 610021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang LiDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, 37 GuoXueXiang, Chengdu, 610041, People’s Republic of ChinaEmail xiangli87@hotmail.comObjective: To evaluate the prognostic factors of penile cancer and the utility of prognostic models.Methods: We analyzed postoperatively collected data of 311 patients diagnosed with penile cancer. Survival analysis (Kaplan–Meier and cox regression methods) was performed on this cohort. The c-index was used to determine the predictive accuracies of potential prognostic factors. The accuracies of four prognostic models were also evaluated, which were AJCC prognostic stage group for three recent editions, and four nomograms constructed by the Surveillance, Epidemiology, and End Results program (SEER). Two novel nomograms using our data were created and AUC of 2-year survival were determined to compare existing and newly established models.Results: Tumor site, T and N stages, nuclear grade and lymph vascular invasion (LVI) significantly influenced prognosis. The 8th T and N stages had better c-indexes than former editions, while no improvement was seen in the 8thAJCC stage group. 6th AJCC+grade nomogram had a higher c-index than other three nomograms (SEER+grade, 6th TNM+grade, and 6th T1-3N0-3+grade nomograms; c-index: 0.831 vs 0.738, 0.792 and 0.781). New nomogram 1 included the 8th T and N stages, tumor site, nuclear grade, and LVI, with a c-index of 0.870. Novel nomogram 2 replaced the T and N stages with the AJCC stage group, which had a lower c-index of 0.855. The order of prediction accuracy of 2-year survival in the old and new models is consistent with the c-index results.Conclusion: Tumor site, stages, grade, and LVI play important roles in predicting survival of penile cancer. The 8th stages have better predictive accuracy than former editions. We proposed two models with better predictive accuracy than former models; specifically, nomogram 1 may be a more precise and convenient tool for predicting penile cancer outcomes.Keywords: penile cancer, TNM stage, survival, nomogram, external validation

Jin Peng,1 Ruiying Dong,1 Jianfen Jiao,1 Min Liu,1 Xi Zhang,1 Hualei Bu,1 Ping Dong,2 Shasha Zhao,3 Naidong Xing,4 Shuai Feng,5 Xingsheng Yang,1 Beihua Kong1 1Department of Obstetrics and Gynecology, Qilu hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China; 2Department of Anesthesiology, Qilu Hospital, Shandong University, Jinan, People’s Republic of China; 3Department of Clinical Nutrition, Qilu Hospital, Shandong University, Jinan, People’s Republic of China; 4Department of Urology, Qilu Hospital, Shandong University, Jinan, People’s Republic of China; 5Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People’s Republic of ChinaCorrespondence: Xingsheng YangDepartment of Obstetrics and Gynecology, Qilu Hospital, Shandong University, No. 107 West Wenhua Road, Jinan, 250001, People’s Republic of ChinaEmail xingshengyang@sdu.edu.cnObjective: Enhanced recovery after surgery (ERAS) protocol has widely gained acceptance in gynecological surgery. Its safety and efficacy should be evaluated fully via well-designed, randomized, control trials. The main objective of our study is to compare the ERAS protocol with the conventional perioperative care program after gynecological oncology. Furthermore, the secondary objectives of our study are the identification of markers that allow us to evaluate the effectiveness of the application of ERAS elements in the modulation of the body’s response to surgical stress.Methods: Patients with gynecological tumors indicated for surgery were randomly assigned to either the ERAS group or the conventional group. The ERAS protocol included short fasting time, fluid restriction, early oral feeding, reduced opioid consumption and immediate mobilization after surgery. The primary endpoint was the reduction of hospital stay in the ERAS group. The day of first flatus, postoperative nausea and vomiting (PONV), maximum pain score by the visual analogue scale (VAS) and complication, readmission rate, reoperation rate, postoperative mortality, total hospital cost and systemic inflammatory response (SIR) were secondary endpoints.Results: A total of 130 patients in gynecological tumor surgery were enrolled (ERAS = 65, conventional = 65). The ERAS group had faster bowel function recovery, significantly less pain, less PONV, shorter hospital stay, and less total hospital costs. SIR markers were estimated and screened out that postoperative platelet, neutrophil-lymphocyte-ratio (NLR) and platelet-lymphocyte-ratio (PLR) were significantly lower in ERAS groups compared to conventional groups.Conclusion: The implementation of ERAS protocol is safe and enhances postoperative recovery after gynecological oncology surgery. We firstly reveal the beneficial effect of ERAS protocols on the alleviation of postoperative SIR, which is a reflection of the magnitude of surgical trauma. Postoperative platelet, NLR or PLR could be the novel and inexpensive markers to assess how ERAS protocols modulate gynecological oncology surgery.Trial Registration: The trial was registered in ClinicalTrials.gov (NCT03629626).Keywords: ERAS, enhanced recovery after surgery, systemic inflammatory response, gynecological oncology surgery, NLR, neutrophil-lymphocyte-ratio, PLR, platelet-lymphocyte-ratio

Hong Li, Kehong Bi, Saran Feng, Yan Wang, Chuansheng Zhu Department of Hematology, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, 250014, ChinaCorrespondence: Kehong BiDepartment of Hematology, Shandong Qianfoshan Hospital, Cheeloo College of Medicine, Shandong University, No. 16766 Jingshi Road, Jinan City, Shandong Province, 250014, ChinaEmail KehongBiRoad@163.comPurpose: CircRNA circ_POLA2 has been reported as an oncogene in lung cancer, while its role in other malignancies is unknown. This study aimed to explore the role of circ_POLA2 in acute myeloid leukemia (AML).Methods: The expression levels of circ_POLA2, mature miR-34a and miR-34a precursor in bone marrow mononuclear cells (BMMNCs) from AML patients (n = 50) and healthy controls (n = 50) were determined by RT-qPCR. Correlations among them were analyzed by Pearson’s correlation coefficient. Overexpression of circ_POLA2 was achieved in AML cell lines, followed by the measurement of the expression levels of mature miR-34a and miR-34a precursor. The role of circ_POLA2 and miR-34a in regulating AML cell proliferation was assessed by CCK-8 assay.Results: Circ_POLA2 was upregulated in AML and inversely correlated with mature miR-34a, but not miR-34a precursor. In AML cells, overexpression of circ_POLA2 decreased the expression levels of mature miR-34a, but not miR-34a precursor. Cell proliferation analysis showed that the overexpression of miR-34a attenuated the effects of overexpression of circ_POLA2 on cell proliferation.Conclusion: Circ_POLA2 is upregulated in AML and promotes cell proliferation by suppressing the production of mature miR-34a.Keywords: circ_POLA2, acute myeloid leukemia, miR-34a, maturation

Zheng Wang,1,* Xiaoxi Wang,2,* Fei Cheng,2 Xue Wen,2 Shi Feng,2 Fang Yu,2 Hui Tang,2 Zhengjin Liu,3 Xiaodong Teng2 1Department of Neurology, Hangzhou Seventh People’s Hospital, Hangzhou, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 3Department of Pathology, Zhongshan Hospital, Xiamen University, Xiamen, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zhengjin LiuDepartment of Pathology, Zhongshan Hospital, Xiamen University, 201 Hubin South Road, Xiamen, Fujian, 361004, People’s Republic of ChinaEmail liuzhengjin@163.comXiaodong TengDepartment of Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, 310000, People’s Republic of ChinaEmail teng1102069@zju.edu.cnBackground: Glioma is a common intracranial malignant tumor with high rates of invasiveness and mortality. This study aimed to investigate the mechanism of rapamycin in glioma.Methods: U118-MG cells were treated with and without rapamycin in vivo and then collected for RNA sequencing. Differentially expressed miRNAs (DEMs) were screened and verified. MiR-26a-5p was selected for functional verification, and the target gene of miR-26a-5p was identified. The effects of miR-26a-5p on cell proliferation, cell cycle, apoptosis, and autophagy were also investigated.Results: In total, 58 up-regulated and 41 down-regulated DEMs were identified between rapamycin-treated and untreated U118-MG cells. MiR-26-5p levels were up-regulated in U118-MG cells treated with 12.5 μM rapamycin, and death-associated protein kinase 1 (DAPK1) expression, a direct miR-26a-5p target gene, was down-regulated. Rapamycin substantially inhibited cell proliferation and cell percentage in the S phase and promoted cell apoptosis; miR-26a-5p inhibitor increased cell proliferation and cell cycle and decreased cell apoptosis; DAPK1 overexpression further induced cell proliferation, increased the cell number in the S phase, and inhibited apoptosis in glioma cells. Notably, rapamycin increased the autophagy-related Beclin1 protein expression levels and the LC3 II/I ratio.Conclusion: Rapamycin exerts anti-tumor effects by promoting autophagy in glioma cells, which was dependent on the miR-26a-5p/DAPK1 pathway activation by rapamycin.Keywords: rapamycin, autophagy, RNA sequencing, glioma cells, miR-26a-5p, death-associated protein kinase 1

Shanglong Feng,1,* Li Zhou,2,* Xinhui Zhang,1,* Baolin Tang,2 Xiaoyu Zhu,2 Huilan Liu,2 Zimin Sun,2 Changcheng Zheng1,2 1Department of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei, People’s Republic of China; 2Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Changcheng ZhengDepartment of Hematology, Anhui Provincial Hospital, Anhui Medical University, Hefei 230001, People’s Republic of ChinaTel/fax +86-551-62284476Email zhengchch1123@ustc.edu.cnBackground: Hyperleukocytic acute myeloid leukemia (AML) (initial white blood cell count≥100 × 109/L) is a clinical emergency often accompanied by leukostasis syndrome, tumor lysis syndrome (TLS), and disseminated intravascular coagulation (DIC), with a poor clinical prognosis. The aim of this study retrospectively analyzed the clinical features of hyperleukocytic AML, focusing on high-risk factors affecting prognosis, the selection of initial induction therapy, and the impact of hematopoietic stem cell transplantation (HSCT) on prognosis.Patients and methods: A total of 558 AML patients at our center from January 2013 to December 2017 were diagnosed, and 52 (9.32%) patients presented with hyperleukocytosis were retrospectively reviewed.Results: The 3-year overall survival (OS) rate in the 15–39 years old and 40–60 years old group was 58.8% and 25.4%, respectively; the longest survival time in patients aged >60 years was only 8 months, and the 8-month OS rate was 8.3% (p=0.002). The 3-year OS rate of the patients in the favorable risk group, intermediate risk group and high risk group, according to the 2017 ELN risk stratification, was 50%, 28.0%, and 29.5%, respectively (p=0.374). The 3-year OS rate of patients carrying CEBPA or NPM1 mutation and those with FLT3-ITD or MLL mutation was 37.5% and 30.0%, respectively (p=0.63). The 3-year OS rate of patients employing an induction regimen of a standard IA regimen was 58.4%, and of those employing a non-standard IA regimen was 22.2% (p=0.065). The 3-year OS rate of the transplantation patients reached 73.8%, while the 9-month OS rate of patients without transplantation was 11.4% (p

Di Lu,* Zhizhi Wang,* Xiguang Liu,* Siyang Feng, Xiaoying Dong, Xiaoshun Shi, He Wang, Hua Wu, Gang Xiong, Haofei Wang, Kaican Cai Department of Thoracic Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China *These authors contributed equally to this work Purpose: A survival improvement was achieved with adjuvant chemotherapy in non-small-cell lung cancer (NSCLC) patients, but its differential effects among patients with different stages remained controversial. This study aimed to compare the beneficial effects of adjuvant tyrosine kinase inhibitor (TKI) therapy with those of traditional therapy on NSCLC patients, specifically on EGFR-mutant and stage II–IIIA patients, who might benefit most from such treatment.Methods: MEDLINE, Embase, and the Cochrane Library were searched, and the results were screened independently according to certain criteria by two authors. Disease-free survival (DFS) and overall survival (OS) with HRs were used as the summary statistics.Results: A total of 2,915 publications were identified and screened. Six randomized control trials and three retrospective cohort studies of 2,467 patients with acceptable quality were included. The overall EGFR mutation rate was 48.62%. DFS was significantly improved in all the patients (HR, 0.77; 95% CI, 0.68–0.88) and in the subgroup of EGFR-mutant patients (HR, 0.49; 95% CI, 0.40–0.61). The difference of 5-year OS in the subgroup of EGFR-mutant patients (HR, 0.48; 95% CI, 0.31–0.72) was statistically significant, while in all the patients (HR, 1.01; 95% CI, 0.85–1.19), the difference was not significant. In the subgroups of studies in which 30% of patients were in stage IIIA (HR, 0.46; 95% CI, 0.35–0.60), DFS was significantly improved, while in the subgroups of studies in which 50% of patients were in stage I (HR, 0.90; 95% CI, 0.77–1.04), DFS was not significantly improved.Conclusion: Stage IIIA NSCLC patients might benefit more from adjuvant TKIs than stage I NSCLC patients after radical resection. Keywords: non-small-cell lung cancer, EGFR tyrosine kinase inhibitor, adjuvant therapy, meta-analysis

Jianqin Shen,1 Huiyan Li,1 Shi Feng,2 Hongguang Cui1 1Department of Ophthalmology, 2Department of Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China Purpose: To report the clinical features, imaging manifestations, histopathology, and immunohistochemical features of several cases of orbital solitary fibrous tumors (SFTs) in a Chinese tertiary hospital, and to undertake a literature review of this rare disease. Methods: A non-comparative retrospective review of clinical presentations, imaging manifestations, histopathology, and immunohistochemical features as well as the management and disease outcomes of patients with orbital SFT was conducted along with a review of orbital SFT cases in the literature. Results: This study includes two male and two female patients, with an average age of 53 years. Common presentations among these patients included a palpable subcutaneous mass, swelling of the eyelid, proptosis, diplopia, and vision disturbance. Three patients (cases 2–4) underwent imaging scans. All patients had complete surgical excisions and the ­tissue was subjected to pathological analysis. One patient (Case 4) experienced a recurrence with malignant transformation and received a re-excision surgery and postoperative radiotherapy. All patients remain alive and well after a minimum follow-up of 12 months (range 12–34 months). Conclusion: Despite its rare occurrence, we suggest that the possibility of orbital SFTs needs to be considered when a painless, slowly growing orbital mass is identified. Typical characteristic magnetic resonance imaging features of orbital SFTs are iso- or hypointense signals on T1 and T2-weighted images, with marked enhancement. A positive cluster of differentiation 34 (CD34) staining is an important diagnostic clue favoring SFT. Some orbital SFTs are infiltrating, aggressive, or recur with malignant transformation. Therefore, regular long-term follow-up after complete excision is mandatory. Keywords: orbit, CD34, malignant transformation, MR

Abstract Background To retrospectively analyze the risk factors of liver metastases in patients with gastric cancer in a single center, and to establish a Nomogram prediction model to predict the occurrence of liver metastases. Methods A total of 96 patients with gastric cancer who were also diagnosed with liver metastasis (GCLM) and treated in our center from January 1, 2010 to December 31, 2020 were included. The clinical data of 1095 patients with gastric cancer who were diagnosed without liver metastases (GC) in our hospital from January 1, 2014 to December 31, 2017 were retrospectively compared by univariate and multivariate logistic regression. 309 patients diagnosed with gastric cancer in another medical center from January 1, 2014 to December 31, 2018 were introduced as external validation cohorts. Results Based on the training cohort, multivariate analysis revealed that tumor site (OR = 0.55, P = 0.046), N stage (OR = 4.95, P = 0.004), gender (OR = 0.04, P = 0.001), OPNI (OR = 0.95, P = 0.041), CEA (OR = 1.01, P = 0.018), CA724 (OR = 1.01, P = 0.006), CA242 (OR = 1.01, P = 0.006), WBC (OR = 1.13, P = 0.024), Hb (OR = 0.98, P

Abstract Background Colon cancer (CC) is a malignancy associated with significant morbidity and mortality within the gastrointestinal tract. Recurrence and metastasis are the main factors affecting the prognosis of CC patients undergoing radical surgery; consequently, we attempted to determine the impact of immunity-related genes. Result We constructed a CC risk model based on ZG16, MPC1, RBM47, SMOX, CPM and DNASE1L3. Consistently, we found that a significant association was found between the expression of most characteristic genes and tumor mutation burden (TMB), microsatellite instability (MSI) and neoantigen (NEO). Additionally, a notable decrease in RBM47 expression was observed in CC tissues compared with that in normal tissues. Moreover, RBM47 expression was correlated with clinicopathological characteristics and improved disease-free survival (DFS) and overall survival (OS) among patients with CC. Lastly, immunohistochemistry and co-immunofluorescence staining revealed a clear positive correlation between RBM47 and CXCL13 in mature tertiary lymphoid structures (TLS) region. Conclusion We conclude that RBM47 was identified as a prognostic-related gene, which was of great significance to the prognosis evaluation of patients with CC and was correlated with CXCL13 in the TLS region.

Objective: Circulating tumor DNA (ctDNA) is increasingly being used as a potential prognostic biomarker in cancer patients. We aimed to assess the prognostic value of ctDNA in different subtypes of breast cancer patients throughout the whole treatment cycle. Materials and methods: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov databases were searched from January 2016 to May 2022. The following search terms were used: ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma. Only studies written in English were included. The following pre-specified criteria should be met for inclusion: (i) original articles, conference abstracts, etc.; (ii) patients with breast cancer; (iii) ctDNA measurement; and (iv) clinical outcome data such as recurrence-free survival (RFS) and overall survival (OS). The random-effects model was preferred considering the potential heterogeneity across studies. The main outcomes are ctDNA detection rate and postoperative long-term outcomes (RFS and OS). Results: A total of 24 studies were screened. At every measurement time, the ctDNA detection rate of the HR+ subgroup was similar to that of the HR- subgroup (P = 0.075; P = 0.458; P = 0.744; and P = 0.578), and the ctDNA detection rate of the HER2+ subgroup was similar to that of the HER2- subgroup (P = 0.805; P = 0.271; P = 0.807; and P = 0.703). In the HR+ subgroup, RFS and OS of ctDNA positive patients were similar to those of ctDNA negative patients (P = 0.589 and P = 0.110), while RFS and OS of the ctDNA positive group was significantly shorter than those of the ctDNA negative patients in the HR- subgroup (HR = 4.03, P < 0.001; HR = 3.21, P < 0.001). According to HER grouping, the results were the same as above. In the triple negative breast cancer (TNBC) subgroup, the RFS and OS of ctDNA-positive patients was significantly shorter than of the ctDNA negative patients before and after surgery. Conclusions: ctDNA was more predictive of recurrence-free survival and overall survival in the HR- subgroup than in the HR+ subgroup, and the same result was showed in the HER2- subgroup vs. HER2+ subgroup. The prognosis of the TNBC subtype is closely related to ctDNA before and after surgery.

Introduction: Although programmed death ligand 1 (PD-L1) inhibitor plus chemotherapy regimen is a promising strategy for malignant tumors, it can induce significant immune-related adverse events, such as immune-related pneumonitis. Here, we report the first case of lethal immune-related pneumonitis in an Asian patient receiving anti-PD-L1 treatment. Case Presentation: A 68-year-old man was diagnosed with small cell lung cancer and interstitial pneumonia. After his pulmonary infection was relieved by comprehensive treatment, the patient received first-line treatment with durvalumab plus etoposide and carboplatin. Two weeks after starting durvalumab treatment, the patient had chest pain and shortness of breath. He was diagnosed with immune-induced pneumonia and treated with methylprednisolone, cefoperazone, and sulbactam, followed by oxygen and pirfenidone. Oxygen partial pressure decreased to 58 mm Hg within next the 4 days and laboratory assessment suggested cytokine storm. The patient underwent 2 plasma exchanges, one double filtration plasmapheresis and oxygen saturation decreased continuously. The patient died 1 month after durvalumab treatment. Conclusion: Immune-related pneumonitis induced by PD-L1 inhibitors is rare but life-threatening. Infection should be ruled out before starting immunotherapy.

Abstract Objective Mitosis karyorrhexis index (MKI) can reflect the proliferation status of neuroblastoma cells. This study aimed to investigate the contrast-enhanced computed tomography (CECT) radiomics features associated with the MKI status in neuroblastoma. Materials and methods 246 neuroblastoma patients were retrospectively included and divided into three groups: low-MKI, intermediate-MKI, and high-MKI. They were randomly stratified into a training set and a testing set at a ratio of 8:2. Tumor regions of interest were delineated on arterial-phase CECT images, and radiomics features were extracted. After reducing the dimensionality of the radiomics features, a random forest algorithm was employed to establish a three-class classification model to predict MKI status. Results The classification model consisted of 5 radiomics features. The mean area under the curve (AUC) of the classification model was 0.916 (95% confidence interval (CI) 0.913–0.921) in the training set and 0.858 (95% CI 0.841–0.864) in the testing set. Specifically, the classification model achieved AUCs of 0.928 (95% CI 0.927–0.934), 0.915 (95% CI 0.912–0.919), and 0.901 (95% CI 0.900–0.909) for predicting low-MKI, intermediate-MKI, and high-MKI, respectively, in the training set. In the testing set, the classification model achieved AUCs of 0.873 (95% CI 0.859–0.882), 0.860 (95% CI 0.852–0.872), and 0.820 (95% CI 0.813–0.839) for predicting low-MKI, intermediate-MKI, and high-MKI, respectively. Conclusions CECT radiomics features were found to be correlated with MKI status and are helpful for reflecting the proliferation status of neuroblastoma cells.

ObjectiveLung cancer, the most prevalent malignancy, is typically diagnosed at an advanced stage. Smoking is a pivotal risk factor for NSCLC, yet the impact of various smoking statuses on NSCLC remains unclear. Thus, this study aims to explore whether different smoking statuses can causally influence NSCLC through effects on predictive targets, offering a novel perspective for NSCLC treatment.MethodsEmploying dual-sample MR, MVMR, and TSMR approaches, we assessed the causal relationships between 13 distinct smoking statuses and NSCLC, using predicted potential therapeutic targets as mediators to further elucidate the causal interplay among them.ResultsAmong the 13 smoking statuses, current tobacco smoking, exposure to tobacco smoke outside the home, past tobacco smoking, and never smoked demonstrated causal relationships with NSCLC. MVMR analysis reveals that Current tobacco smoking is an independent risk factor for NSCLC. Utilizing NCAPD2, IL11RA, and MLC1 as mediators, IL11RA (22.2%) was found to potentially mediate the relationship between past tobacco smoking and NSCLC.ConclusionThis study, integrating bioinformatics and MR analysis, identified three potential predictive targets as mediators to investigate the causal relationships between different smoking statuses and NSCLC through potential therapeutic targets, providing new insights for the treatment and prevention of NSCLC.

Objective: Circulating tumor DNA (ctDNA) is increasingly being used as a potential prognosis biomarker in patients of breast cancer. This review aims to assess the clinical value of ctDNA in outcome prediction in breast cancer patients throughout the whole treatment cycle. Methods: PubMed, Web of Science, Embase, Cochrane Library, Scopus, and clinical trials.gov were searched from January 2016 to May 2022. Conference abstracts published in last three years were also included. The following search terms were used: ctDNA OR circulating tumor DNA AND breast cancer OR breast carcinoma. Only studies written in English languages were included. The following pre-specified criteria should be met for inclusion: (1) observational studies (prospective or retrospective), randomized control trials, case-control studies and case series studies; (2) patients with breast cancer; (3) ctDNA measurement; (4) clinical outcome data such as objective response rate (ORR), pathological complete response (pCR), relapse-free survival (RFS), overall survival (OS), and so on. The random-effect model was preferred considering the potential heterogeneity across studies. The primary outcomes included postoperative short-term outcomes (ORR and pCR) and postoperative long-term outcomes (RFS, OS, and relapse). Secondary outcomes focused on ctDNA detection rate. Results: A total of 30 studies, comprising of 19 cohort studies, 2 case-control studies and 9 case series studies were included. The baseline ctDNA was significantly negatively associated with ORR outcome (Relative Risk [RR] = 0.65, 95% confidence interval [CI]: 0.50–0.83), with lower ORR in the ctDNA-positive group than ctDNA-negative group. ctDNA during neoadjuvant therapy (NAT) treatment was significantly associated with pCR outcomes (Odds Ratio [OR] = 0.15, 95% CI: 0.04–0.54). The strong association between ctDNA and RFS or relapse outcome was significant across the whole treatment period, especially after the surgery (RFS: Hazard Ratio [HR] = 6.74, 95% CI: 3.73–12.17; relapse outcome: RR = 7.11, 95% CI: 3.05–16.53), although there was heterogeneity in these results. Pre-operative and post-operative ctDNA measurements were significantly associated with OS outcomes (pre-operative: HR = 2.03, 95% CI: 1.12–3.70; post-operative: HR = 6.03, 95% CI: 1.31–27.78). Conclusions: In this review, ctDNA measurements at different timepoints are correlated with evaluation indexes at different periods after treatment. The ctDNA can be used as an early potential postoperative prognosis biomarker in breast cancer, and also as a reference index to evaluate the therapeutic effect at different stages.

Background: Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China. Most HCC patients have the complications of chronic liver disease and need overall consideration and whole-course management, including diagnosis, treatment, and follow-up. To develop a reasonable, long-term, and complete management plan, multiple factors need to be considered, including the patient’s general condition, basic liver diseases, tumor stage, tumor biological characteristics, treatment requirements, and economic cost. Summary: To better guide the whole-course management of HCC patients, the Chinese Association of Liver Cancer and the Chinese Medical Doctor Association has gathered multidisciplinary experts and scholars in relevant fields to formulate the “Chinese Expert Consensus on The Whole-Course Management of Hepatocellular Carcinoma (2023).” Key Messages: This expert consensus, based on the current clinical evidence and experience, proposes surgical and nonsurgical HCC management pathways and involves 18 recommendations, including perioperative treatment, systematic treatment combined with local treatment, conversion treatment, special population management, symptomatic support treatment, and follow-up management.

Abstract Background Accurate identification of extrahepatic cholangiocarcinoma (ECC) from an image is challenging because of the small size and complex background structure. Therefore, considering the limitation of manual delineation, it’s necessary to develop automated identification and segmentation methods for ECC. The aim of this study was to develop a deep learning approach for automatic identification and segmentation of ECC using MRI. Methods We recruited 137 ECC patients from our hospital as the main dataset (C1) and an additional 40 patients from other hospitals as the external validation set (C2). All patients underwent axial T1-weighted imaging (T1WI), T2-weighted imaging (T2WI), and diffusion-weighted imaging (DWI). Manual delineations were performed and served as the ground truth. Next, we used 3D VB-Net to establish single-mode automatic identification and segmentation models based on T1WI (model 1), T2WI (model 2), and DWI (model 3) in the training cohort (80% of C1), and compared them with the combined model (model 4). Subsequently, the generalization capability of the best models was evaluated using the testing set (20% of C1) and the external validation set (C2). Finally, the performance of the developed models was further evaluated. Results Model 3 showed the best identification performance in the training, testing, and external validation cohorts with success rates of 0.980, 0.786, and 0.725, respectively. Furthermore, model 3 yielded an average Dice similarity coefficient (DSC) of 0.922, 0.495, and 0.466 to segment ECC automatically in the training, testing, and external validation cohorts, respectively. Conclusion The DWI-based model performed better in automatically identifying and segmenting ECC compared to T1WI and T2WI, which may guide clinical decisions and help determine prognosis.

Abstract Background We used a genome‐wide discovery approach to identify methylation markers associated with metastasis in men with localized prostate cancer (PCa), as better identification of those at high risk of metastasis can inform treatment decision‐making. Methods We identified men with localized PCa at Kaiser Permanente California (January 1, 1997–December 31, 2006) who did not receive curative treatment and followed them for 10 years to determine metastasis status. Cases were chart review‐confirmed metastasis, and controls were matched using density sampling. We extracted DNA from the cancerous areas in the archived diagnostic tissue blocks. We used Illumina's Infinium MethylationEPIC BeadChip for methylation interrogation. We used conditional logistic regression and Bonferroni's correction to identify methylation markers associated with metastasis. In a separate validation cohort (2007), we evaluated the added predictive utility of the methylation score beyond clinical risk score. Results Among 215 cases and 404 controls, 31 CpG sites were significantly associated with metastasis status. Adding the methylation score to the clinical risk score did not meaningfully improve the c‐statistic (0.80–0.81) in the validation cohort, though the score itself was statistically significant (p

Objective: The incidence and mortality of hepatocellular carcinoma (HCC) have been increasing around the world. Current guidelines recommend HCC screening in high-risk population. However, the strength of evidence of benefits and harms of HCC screening to support the recommendation was unclear. The objective is to systematically synthesize current evidence on the benefits and harms of HCC screening. Methods: We searched PubMed and nine other databases until August 20, 2021. We included cohort studies and RCTs that compared the benefits and harms of screening and non-screening in high-risk population of HCC. Case series studies that reported harms of HCC screening were also included. Pooled risk ratio (RR), according to HCC screening status, was calculated for each benefit outcome (e.g., HCC mortality, survival rate, proportion of early HCC), using head-to-head meta-analysis. The harmful outcomes (e.g., proportion of physiological harms provided by non-comparative studies were pooled by prevalence of meta-analysis. Analysis on publication bias and quality of life, subgroup analysis, and sensitivity analysis were also conducted. Results: We included 70 studies, including four random clinical trials (RCTs), 63 cohort studies,three case series studies. The meta-analysis of RCTs showed HCC screening was significantly associated with reduced HCC mortality (RR [risk ratio], 0.73 [95% CI, 0.56–0.96]; I2 = 75.1%), prolonged overall survival rates (1-year, RR, 1.72 [95% CI, 1.13–2.61]; I2 = 72.5%; 3-year, RR, 2.86 [95% CI, 1.78–4.58]; I2 = 10.1%; and 5-year, RR, 2.76 [95% CI, 1.37–5.54]; I2 = 28.3%), increased proportion of early HCC detection (RR, 2.68 [95% CI, 1.77–4.06]; I2 = 50.4%). Similarly, meta-analysis of cohort studies indicated HCC screening was more effective than non-screening. However, pooled proportion of physiological harms was 16.30% (95% CI: 8.92%–23.67%) and most harms were of a mild to moderate severity. Conclusion: The existing evidence suggests HCC screening is more effective than non-screening in high-risk population. However, harms of screening should not be ignored.

Background and Objective: Bone tumors present significant challenges in orthopedic medicine due to variations in clinical treatment approaches for different tumor types, which includes benign, malignant, and intermediate cases. Convolutional Neural Networks (CNNs) have emerged as prominent models for tumor classification. However, their limited perception ability hinders the acquisition of global structural information, potentially affecting classification accuracy. To address this limitation, we propose an optimized deep learning algorithm for precise classification of diverse bone tumors. Materials and Methods: Our dataset comprises 786 computed tomography (CT) images of bone tumors, featuring sections from two distinct bone species, namely the tibia and femur. Sourced from The Second Affiliated Hospital of Fujian Medical University, the dataset was meticulously preprocessed with noise reduction techniques. We introduce a novel fusion model, VGG16-ViT, leveraging the advantages of the VGG-16 network and the Vision Transformer (ViT) model. Specifically, we select 27 features from the third layer of VGG-16 and input them into the Vision Transformer encoder for comprehensive training. Furthermore, we evaluate the impact of secondary migration using CT images from Xiangya Hospital for validation. Results: The proposed fusion model demonstrates notable improvements in classification performance. It effectively reduces the training time while achieving an impressive classification accuracy rate of 97.6%, marking a significant enhancement of 8% in sensitivity and specificity optimization. Furthermore, the investigation into secondary migration's effects on experimental outcomes across the three models reveals its potential to enhance system performance. Conclusion: Our novel VGG-16 and Vision Transformer joint network exhibits robust classification performance on bone tumor datasets. The integration of these models enables precise and efficient classification, accommodating the diverse characteristics of different bone tumor types. This advancement holds great significance for the early detection and prognosis of bone tumor patients in the future.

Abstract Background Hepatocellular carcinoma (HCC) generally arises from a background of liver cirrhosis (LC). Patients with cirrhosis and suspected HCC are recommended to undergo serum biomarker tests and imaging diagnostic evaluation. However, the performance of routine diagnostic methods in detecting early HCC remains unpromising. Methods Here, we conducted a large-scale, multicenter study of 1675 participants including 490 healthy controls, 577 LC patients, and 608 HCC patients from nine clinical centers across nine provinces of China, profiled gene mutation signatures of cell-free DNA (cfDNA) using Circulating Single-Molecule Amplification and Resequencing Technology (cSMART) through detecting 931 mutation sites across 21 genes. Results An integrated diagnostic model called “Combined method” was developed by combining three mutation sites and three serum biomarkers. Combined method outperformed AFP in the diagnosis of HCC, especially early HCC, with sensitivities of 81.25% for all stages and 66.67% for early HCC, respectively. Importantly, the integrated model exhibited high accuracy in differentiating AFP-negative, AFP-L3-negative, and PIVKA-II-negative HCCs from LCs.

Abstract Background Solid pulmonary nodules are different from subsolid nodules and the diagnosis is much more challenging. We intended to evaluate the diagnostic and prognostic value of radiomics and deep learning technologies for solid pulmonary nodules. Methods Retrospectively enroll patients with pathologically-confirmed solid pulmonary nodules and collect clinical data. Obtain pre-treatment high-resolution thoracic CT and manually delineate the nodule in 3D. Then, all patients were randomly divided into training and testing sets at a ratio of 7:3, and convolutional neural networks (CNN) models and random forest (RF) models were established. Survival analyses were performed for patients with solid adenocarcinomas. Results Totally 720 solid pulmonary nodules were enrolled, 348 benign and 372 malignant. The CNN model with clinical features achieved the highest AUC [0.819, 95% confidence interval (CI): 0.760–0.877] with a sensitivity of 0.778, specificity of 0.788 and accuracy of 0.783. No significant differences were observed between the CNN and radiomics models. There were 295 solid adenocarcinomas in survival analysis. Different disease-free survival was observed between the low-risk and high-risk groups divided according to the radiomics Rad-score. However, the groups based on deep learning signatures showed similar survival. Cox regression analysis indicated that the radiomics Rad-score (hazard ratio: 5.08, 95% CI: 2.61–9.90) was an independent predictor of recurrence. Conclusions The radiomics and deep learning models can well predict the malignancy of solid pulmonary nodules. Radiomics signatures also demonstrate prognostic value in solid adenocarcinomas.

Abstract Background Several methods can assist in detecting early esophageal cancer (EEC) and staging esophageal cancer (EC) invasion depth. Objective To evaluate the accuracy of magnifying endoscopy with narrow-band imaging (ME-NBI) plus endoscopic ultrasonography (EUS) for diagnosing EC. Methods We searched the PubMed, Embase, Cochrane Library, and China National Knowledge Infrastructure (CNKI) databases for relevant studies. The Quality Assessment of Diagnostic Accuracy Studies 2 (QADAS2) was used to assess the studies’ methodological quality. The sensitivity, specificity, positive likelihood (LR+), negative likelihood (LR−), and diagnostic odds ratio (DOR) were calculated, and the summary receiver operating characteristic (SROC) curves were drawn to evaluate the diagnostic performance. Results Seven studies were included. The meta-analysis suggested that the pooled sensitivity, specificity, LR+, LR−, and DOR of ME-NBI plus EUS for diagnosing EC were 0.947 (95% confidence interval [CI], 0.901–0.975), 0.894 (95% CI, 0.847–0.931), 7.989 (95% CI, 4.264–14.970), 0.066 (95% CI, 0.035–0.124), and 137.96 (95% CI, 60.369–315.27), respectively. Those values for staging the invasive depth were 0.791 (95% CI, 0.674–0.881), 0.943 (95% CI, 0.906–0.968), 13.087 (95% CI, 7.559–22.657), 0.226 (95% CI, 0.142–0.360), and 61.332 (95% CI, 27.343–137.57). The areas under the curves (AUCs) for diagnosis and staging were 0.97 and 0.95, respectively. Conclusions ME-NBI plus EUS might be an adequate diagnostic and staging modality for EC. Due to the study limitations, more large-scale, high-quality studies are needed to confirm the diagnostic accuracy of ME-NBI plus EUS.

Abstract Background The clinical application of robotic-assisted gastrectomy remains controversial, especially as clinical studies of this operation navigated by carbon nanoparticle suspension injection (CNSI) have not been conducted. This study aims to assess the perioperative safety and efficacy of CNSI-guided robotic-assisted gastrectomy in patients with gastric cancer by focusing on short-term outcomes. Methods A retrospective analysis of patients who underwent CNSI-guided laparoscopic or robotic-assisted gastrectomy with a pathological diagnosis of gastric cancer was conducted. Data on demographics, surgical management, clinical-pathological results and short-term outcomes were compared among the groups. Results A total of 126 eligible patients were separated into the robotic-assisted gastrectomy (RAG) group (n = 16) and the laparoscopic gastrectomy (LG) group (n = 110) in total. The operation time of the RAG group is longer than the LG group (p = 0.0000). When it comes to perioperative and short-term complications, there exists no statistical difference between the two groups. Conclusion The time required for CNSI-guided robotic-assisted gastrectomy is longer than that for CNSI-guided laparoscopic gastrectomy. CNSI-guided robotic-assisted gastrectomy is safe and effective.

Although the diagnosis of glioma is constantly changing with the update of WHO diagnostic guidelines, the current treatment methods are still mainly surgical treatment, supplemented by radiotherapy and chemotherapy. It is a pity that the treatment effect of high-grade glioma is still unsatisfactory. How to improve the prognosis of patients is the key problem in the field of medical exploration of glioma. It is gratifying that many new ideas and methods have emerged in the diagnosis and treatment of glioma, in which some trials represented by tumor treating fields have achieved good results in clinical research, moreover, the fields of immunotherapy and targeted therapy have developed too. This paper aims to share and explore these new methods and summarize the progress of diagnosis and treatment of glioma.

Background and AimThe prediction models of postoperative survival for hepatitis B virus-related hepatocellular carcinoma (HBV-HCC) with microvascular invasion (MVI) have not been well established. The study objective was the development of nomograms to predict disease recurrence and overall survival (OS) in these patients.MethodsData were obtained from 1046 HBV-related MVI-positive HCC patients who had undergone curative resection from January 2014 to December 2017. The study was approved by the Eastern Hepatobiliary Surgery Hospital and Jinling Hospital ethics committee, and patients provided informed consent for the use of their data. Nomograms for recurrence and OS were created by Cox regression model in the training cohort (n=530). The modes were verified in an internal validation cohort (n= 265) and an external validation cohort (n= 251).ResultsThe nomograms of recurrence and OS based on preoperative serological indicators (HBV-DNA, neutrophil-lymphocyte ratio, a-fetoprotein), tumor clinicopathologic features (diameter, number), surgical margin and postoperative adjuvant TACE achieved high C-indexes of 0.722 (95% confidence interval [CI], 0.711-0.732) and 0.759 (95% CI, 0.747-0.771) in the training cohort, respectively, which were significantly higher than conventional HCC staging systems (BCLC, CNLC, HKLC).The nomograms were validated in the internal validation cohort (0.747 for recurrence, 0.758 for OS) and external validation cohort(0.719 for recurrence, 0.714 for OS) had well-fitted calibration curves. Our nomograms accurately stratified patients with HBV-HCC with MVI into low-, intermediate- and high-risk groups of postsurgical recurrence and mortality. Prediction models for recurrence-free survival (https://baishileiehbh.shinyapps.io/HBV-MVI-HCC-RFS/) and OS (https://baishileiehbh.shinyapps.io/HBV-MVI-HCC-OS/) were constructed.ConclusionsThe two nomograms showed good predictive performance and accurately distinguished different recurrence and OS by the nomograms scores for HBV-HCC patients with MVI after resection.

Background: Primary liver cancer, around 75%–85% are hepatocellular carcinoma in China, is the fourth most common malignancy and the second leading cause of tumor-related death, thereby posing a significant threat to the life and health of the Chinese people. Summary: Since the publication of Guidelines for Diagnosis and Treatment of Primary Liver Cancer in China in June 2017, which were updated by the National Health Commission in December 2019, additional high-quality evidence has emerged from researchers worldwide regarding the diagnosis, staging, and treatment of liver cancer, that requires the guidelines to be updated again. The new edition (2022 Edition) was written by more than 100 experts in the field of liver cancer in China, which not only reflects the real-world situation in China, but also may re-shape the nationwide diagnosis and treatment of liver cancer. Key Messages: The new guideline aims to encourage the implementation of evidence-based practice, and improve the national average five-year survival rate for patients with liver cancer, as proposed in the "Health China 2030 Blueprint."

BackgroundThe best choice of first-line treatment for metastatic hormone-sensitive prostate cancer (mHSPC) is unclear. We aimed to compare the effectiveness and safety determined in randomized clinical trials of doublet and triplet treatments for mHSPC.MethodsMedline, Embase, Cochrane Central and ClinicalTrials.gov were searched from inception through July 01, 2022. Eligible studies were phase III randomized clinical trials evaluating androgen deprivation treatment (ADT) alone, doublet therapies [ADT combined with docetaxel (DOC), novel hormonal agents (NHAs), or radiotherapy (RT)], or triplet therapies (NHA+DOC+ADT) as first-line treatments for mHSPC. Outcomes of interest included overall survival (OS), progression-free survival (PFS) and grades 3-5 adverse events (AEs). Subgroup analyses were performed based on tumor burden. The effects of competing treatments were assessed by Bayesian network meta-analysis using R software.ResultsTen trials with 12,298 patients comparing nine treatments were included. Darolutamide (DARO) +DOC+ADT ranked best in terms of OS benefits (OR 0·52 [95% CI 0·39–0·70]), but its advantages were all statistically insignificant compared with other therapy options except for DOC+ADT (OR 0·68 [95% CI 0·53–0·88]) and RT+ADT (OR 0·57 [95% CI 0·40–0·80]). In terms of PFS, enzalutamide(ENZA)+DOC+ADT (OR 0·32 [95% CI 0·24–0·44]) and abiraterone and prednisone (AAP) +DOC+ADT (OR 0·33 [95% CI 0·25–0·45]) ranked best. For patients with high volume disease (HVD), low volume disease (LVD), and visceral metastases, the optimal therapies were AAP+DOC+ADT (OR 0·52 [95% CI 0·33–0·83]), apalutamide+ADT (OR 0·52 [95% CI 0·26–1·05]) and DARO+DOC+ADT (OR 0·42 [95% CI 0·13–1·34]), respectively. For safety, AAP+DOC+ADT (OR 3·56 [95% CI 1·51–8·43]) ranked worst with the highest risk of grade 3−5 AEs.ConclusionsTriple therapies may further improve OS and PFS but may be associated with a decrease in safety. Triplet therapies could be suggested for HVD patients, while doublet combinations should still be preferred for LVD patients.Systematic Review Registrationhttps://www.crd.york.ac.uk/PROSPEROFILES/303117_STRATEGY_20220202.pdf, identifier CRD4202303117.

Yanmei Dai,1 Huijie Jiang,1 Shi-Ting Feng,2 Yuwei Xia,3 Jinping Li,1 Sheng Zhao,1 Dandan Wang,1 Xu Zeng,1 Yusi Chen,1 Yanjie Xin,1 Dongmin Liu1 1Department of Radiology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang Province, 150086, People’s Republic of China; 2Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong Province, 510030, People’s Republic of China; 3Huiying Medical Technology Co., Ltd, Beijing City, 100192, People’s Republic of ChinaCorrespondence: Huijie Jiang; Shi-Ting Feng, Tel +86 86605576, Email jianghuijie@hrbmu.edu.cn; fengsht@mail.sysu.edu.cnPurpose: This study aims to develop a new model to more comprehensively and accurately predict the survival of patients with HCC after initial TACE.Patients and Methods: The whole cohort (n = 102) was randomly divided into a training cohort and a validation cohort in the ratio of 8:2. The optimal radiomics signatures were screened using the least absolute shrinkage and selection operator algorithm (LASSO) regression for constructing the radscore to predict overall survival (OS). The C-index (95% confidence interval, CI), calibration curve, and decision curve analysis (DCA) were used to evaluate the performance of the models. The independent risk factors (hazard ratio, HR) for predicting OS were stratified by Kaplan–Meier (K-M) analysis and the Log rank test.Results: The median OS was 439 days (95% CI: 215.795– 662.205) in whole cohort, and in the training cohort and validation cohort, the median OS was 552 days (95% CI: 171.172– 932.828), 395 days (95% CI: 309.415– 480.585), respectively (P = 0.889). After multivariate cox regression, the combined radscore-clinical model was consisted of radscore (HR: 2.065, 95% CI: 1.285– 3.316; P = 0.0029) and post-response (HR: 1.880, 95% CI: 1.310– 2.697; P = 0.0007), both of which were independent risk factors for the OS. In the validation cohort, the efficacy of both the radscore (C-index: 0.769, 95% CI: 0.496– 1.000) and combined model (C-index: 0.770, 95% CI: 0.581– 0.806) were higher than that of the clinical model (C-index: 0.655, 95% CI: 0.508– 0.802). The calibration curve of the combined model for predicting OS presented good consistency between observations and predictions in both the training cohort and validation cohort.Conclusion: Noninvasive imaging has a good prediction performance of survival after initial TACE in patients with HCC. The combined model consisting of post-response and radscore may be able to better predict outcome.Keywords: computed tomography, hepatocellular carcinoma, overall survival, radiomics, transarterial chemoembolization

Abstract Introduction Immunotherapy has become a new therapy for advanced hepatocellular carcinoma (HCC); however, its treatment results are considerably different. CD4+ T cells (CD4+) are the key to immunotherapy, but patients with HCC that have low CD4+ are rarely observed for clinical evidence. Hepatitis B virus-related HCC is often accompanied by cirrhosis and portal hypertension; therefore, CD4+ tend to be relatively low in number. TACE is the standard treatment for Barcelona Clinic Liver Cancer (BCLC)-B HCC, which may further reduce the number of CD4 + . Methods This retrospective cohort study further reduced CD4+ by including patients with human immunodeficiency virus (HIV) to observe the relationship between CD4+ and Chronic hepatitis B virus (CHB) induced HCC. A total of 170 BCLC-B HCC patients (42 HIV+) were included. Univariate and multivariate analyses, and artificial neural networks (ANNs) were used to evaluate the independent risk factors for the two-year survival. Results The statistical analysis of the two-year survival rate showed that the main factors influencing survival were liver function and immune indices, including CD4+, platelet, alanine aminotransferase, aspartate aminotransferase, aspartate aminotransferase-to-platelet ratio index, and fibrosis-4 (FIB-4) (P

Portal vein tumor thrombus (PVTT) is very common and it plays a major role in the prognosis and clinical staging of hepatocellular carcinoma (HCC). We have published the first version of the guideline in 2016 and revised in 2018. Over the past several years, many new evidences for the treatment of PVTT become available, especially for the advent of new targeted drugs and immune checkpoint inhibitors which have further improved the prognosis of PVTT. So, the Chinese Association of Liver Cancer and Chinese Medical Doctor Association revised the 2018 version of the guideline to adapt to the development of PVTT treatment. Future treatment strategies for HCC with PVTT in China would depend on new evidences from more future clinical trials.

Abstract Primary lung cancer is one of the most common malignant tumors in China. Approximately 60% of lung cancer patients have distant metastasis at the initial diagnosis, so it is necessary to find new tumor markers for early diagnosis and individualized treatment. Tumor markers contribute to the early diagnosis of lung cancer and play important roles in early detection and treatment, as well as in precision medicine, efficacy monitoring, and prognosis prediction. The pathological diagnosis of lung cancer in small biopsy specimens determines whether there are tumor cells in the biopsy and tumor type. Because biopsy is traumatic and the compliance of patients with multiple biopsies is poor, liquid biopsy has become a hot research direction. Liquid biopsies are advantageous because they are nontraumatic, easy to obtain, reflect the overall state of the tumor, and allow for real-time monitoring. At present, liquid biopsies mainly include circulating tumor cells, circulating tumor DNA, exosomes, microRNA, circulating RNA, tumor platelets, and tumor endothelial cells. This review introduces the research progress and clinical application prospect of liquid biopsy technology for lung cancer.

Abstract Endometriosis, a chronic disorder characterised by the presence of endometrial-like tissue outside the uterus, is associated with iron overload and oxidative stress in the lesion. Although it is well established that iron overload can trigger ferroptosis, the results of previous studies on ferroptosis resistance and ferroptosis in endometriotic lesions are paradoxical. Here, we found that some stromal cells of the cyst walls that were in contact with the cyst fluid underwent ferroptosis. Surprisingly, endometrial stromal cell ferroptosis triggered the production of angiogenic, inflammatory and growth cytokines. In particular, angiogenic cytokines, such as vascular endothelial growth factor A (VEGFA) and interleukin 8 (IL8), promoted human umbilical vein endothelial cell (HUVEC) vascular formation in vitro. Moreover, we found that inhibition of p38 mitogen-activated protein kinase/signal transducer and activator of transcription 6 (p38 MAPK/STAT6) signalling represses VEGFA and IL8 expression when endometrial stromal cells undergo ferroptosis. Notably, VEGFA and IL8 showed localised expression and were significantly upregulated in ectopic lesions compared to control and eutopic endometrium samples from patients with endometriosis. Thus, our study reveals that endometrial stromal cell ferroptosis in the ovarian endometrioma may trigger cytokine secretion and promote angiogenesis of adjacent lesions via paracrine actions to drive the development of endometriosis, providing a rationale for translation into clinical practice and developing drugs for endometriosis.

Hepatocellular carcinoma (HCC) is one of the most malignant cancers worldwide, with high mortality. However, the molecular regulatory mechanisms of liver cancer, especially transcriptional and post-transcriptional mechanisms, should be further studied. Here we used chromatin and cross-linking immunoprecipitation with high throughput sequencing methods (ChIP-seq and CLIP-seq) to capture the global binding profiles on RNAs and DNAs of Enhancer of zeste homolog 2 (EZH2) and its partner Jumonji And AT-Rich Interaction Domain Containing 2 (JARID2) in liver carcinoma cell lines (HepG2) and normal liver cell line (THLE-2), respectively. We also integrated HCC transcriptome data from the TCGA to analyze the expression pattern of bound genes. We found that EZH2 and JARID2 both showed distinct binding profiles between HepG2 and THLE-2 cells. By binding to the primary RNAs, bound transcripts of EZH2 and JARID2 in HepG2 showed significantly increased transcriptional levels in HCC patients. By performing gene set enrichment analysis (GSEA), the bound transcripts were also highly related to HCC development. We also found EZH2 and JARID2 could specifically bind to several long noncoding RNAs (lncRNAs), including H19. By exploring the DNA binding profile, we detected a dramatically repressed DNA binding ability of EZH2 in HepG2 cells. We also found that the EZH2-bound genes showed slightly increased transcriptional levels in HepG2 cells. Integrating analysis of the RNA and DNA binding profiles suggests EZH2 and JARID2 shift their binding ability from DNA to RNA in HepG2 cells to promote cancer development in HCC. Our study provided a comprehensive and distinct binding profile on RNAs and DNAs of EZH2 and JARID2 in liver cancer cell lines, suggesting their potential novel functional manners to promote HCC development.

Background and objective Segmentectomy has gradually become one of the standard surgical methods for small pulmonary nodules with early lung cancer on imaging. This study aimed to investigate the perioperative outcomes of patients who underwent uniport video-assisted thoracoscopic surgery (VATS) segmentectomy for identifying the intersegmental boundary line (IBL) by the near-infrared fluorescence imaging with intravenous indocyanine green (ICG) method or the modified inflation-deflation (MID) method and assess the feasibility and effectiveness of the ICG fluorescence (ICGF)-based method. Methods We retrospectively analyzed the perioperative data in total 198 consecutive patients who underwent uniport VATS segmentectomy between February 2018 and August 2020. With the guidance of preoperative intelligent/interactive qualitative and quantitative analysis-three dimensional (IQQA-3D), the targeted segment structures could be precisely identified and dissected, and then the IBL was confirmed by ICGF-based method or MID method. Clinical effectiveness and postoperative complications of the two methods were evaluated. Results An IBL was visible in 98% of patients by the ICGF-based group, even with the low-doses of ICG. The ICGF-based group was significantly associated with the shorter IBL clear presentation time [(23.59±4.47) s vs (1,026.80±318.34) s] (P0.05). Conclusion The ICGF-based method could highly accurately identify the IBL and make anatomical segmentectomy easier and faster, and therefore has the potential to be a feasible and effective technique to facilitate the quality of uniport VATS segmentectomy.

Zhi Dong,1,&ast; Yingyu Lin,1,&ast; Fangzeng Lin,2,&ast; Xuyi Luo,3 Zhi Lin,1 Yinhong Zhang,1 Lujie Li,1 Zi-Ping Li,1 Shi-Ting Feng,1 Huasong Cai,1 Zhenpeng Peng1 1Department of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People’s Republic of China; 2Department of Interventional Radiology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People’s Republic of China; 3Department of Emergency, Guangzhou First People’s Hospital, Guangzhou, Guangdong, 510180, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huasong Cai; Zhenpeng PengDepartment of Radiology, The First Affiliated Hospital, Sun Yat-Sen University, 58th, The Second Zhongshan Road, Guangzhou, Guangdong, People’s Republic of ChinaTel +86 20-87755766, extension 8471Fax +86 20-87615805Email caihuas@mail.sysu.edu.cn; pengzhp@mail.sysu.edu.cnPurpose: The treatment response to initial conventional transarterial chemoembolization (cTACE) is essential for the prognosis of patients with hepatocellular carcinoma (HCC). This study explored and verified the feasibility of machine-learning models based on clinical data and contrast-enhanced computed tomography (CT) image findings to predict early responses of HCC patients after initial cTACE treatment.Patients and Methods: Overall, 110 consecutive unresectable HCC patients who were treated with cTACE for the first time were retrospectively enrolled. Clinical data and imaging features based on contrast-enhanced CT were collected for the selection of characteristics. Treatment responses were evaluated based on the modified Response Evaluation Criteria in Solid Tumors (mRECIST) by postoperative CT examination within 2 months after the procedure. Python (version 3.70) was used to develop machine learning models. Least absolute shrinkage and selection operator (LASSO) algorithm was applied to select features with the impact on predicting treatment response after the first TACE procedure. Six machine learning algorithms were used to build predictive models, including XGBoost, decision tree, support vector machine, random forest, k-nearest neighbor, and fully convolutional networks, and their performances were compared using receiver operator characteristic (ROC) curves to determine the best performing model.Results: Following TACE, 31 patients (28.2%) were described as responsive to TACE, while 72 patients (71.8%) were nonresponsive to TACE. Portal vein tumor thrombosis type, albumin level, and distribution of tumors within the liver were selected for predictive model building. Among the models, the RF model showed the best performance, with area under the curve (AUC), accuracy, sensitivity, and specificity of 0.802, 0.784, 0.904, and 0.480, respectively.Conclusion: Machine learning models can provide an accurate prediction of the early response of initial TACE treatment for HCC, which can help in individualizing clinical decision-making and modification of further treatment strategies for patients with unresectable HCC.Keywords: hepatocellular carcinoma, transarterial chemoembolization, machine learning, prediction model, treatment response

Abstract Background and aims Although adjuvant transcatheter arterial chemoembolization (TACE) for resected hepatocellular carcinoma (HCC) may improve survival for some patients, identifying which patients can benefit remains challenging. The present study aimed to construct a survival prediction calculator for individualized estimating the net survival benefit of adjuvant TACE for patients with resected HCC. Methods From a multicenter database, consecutive patients undergoing curative resection for HCC were enrolled and divided into the developing and validation cohorts. Using the independent survival predictors in the developing cohort, two nomogram models were constructed for patients with and without adjuvant TACE, respectively, which predictive performance was validated internally and externally by measuring concordance index (C-index) and calibration. The difference between two estimates of the prediction models was the expected survival benefit of adjuvant TACE. Results A total of 2514 patients met the inclusion criteria for the study. The nomogram prediction models for patients with and without adjuvant TACE were, respectively, built by incorporating the same eight independent survival predictors, including portal hypertension, Child–Pugh score, alpha-fetoprotein level, tumor size and number, macrovascular and microvascular invasion, and resection margin. These two prediction models demonstrated good calibration and discrimination, with all the C-indexes of greater than 0.75 in the developing and validation cohorts. A browser-based calculator was generated for individualized estimating the net survival benefit of adjuvant TACE. Conclusions Based on large-scale real-world data, an easy-to-use online calculator can be adopted as a decision aid to predict which patients with resected HCC can benefit from adjuvant TACE.

Abstract Background The safety and efficacy of indocyanine green (ICG) imaging navigational laparoscopic gastrectomy remain controversial. This study is to evaluate the short-term and long-term outcomes of ICG-guided laparoscopic radial gastrectomy in patients with gastric cancer. Methods Consecutive patients with definitive diagnosis of gastric cancer that underwent laparoscopic radical gastrectomy were collected retrospectively. Propensity score matching (PSM) at 1:1 ratio was performed to compare the outcomes of two groups. Results A total of 122 qualified patients were divided into ICG group (n = 34) and non-ICG group (n = 88). PSM yielded 28 patients with comparable baseline characteristics into each group. The number of retrieved lymph node in ICG group was significantly higher than that in non-ICG group (P = 0.0196). There was no statistical difference of perioperative, short-term, and long-term complications between the two groups. Conclusion ICG-guided laparoscopic radical gastrectomy is safe and effective, and ICG-navigated lymphadenectomy improves the number of retrieved lymph nodes for patients with gastric cancer.

BackgroundDifferent pathological subtypes of lung adenocarcinoma lead to different treatment decisions and prognoses, and it is clinically important to distinguish invasive lung adenocarcinoma from preinvasive adenocarcinoma (adenocarcinoma in situ and minimally invasive adenocarcinoma). This study aims to investigate the performance of the deep learning approach based on high-resolution computed tomography (HRCT) images in the classification of tumor invasiveness and compare it with the performances of currently available approaches.MethodsIn this study, we used a deep learning approach based on 3D conventional networks to automatically predict the invasiveness of pulmonary nodules. A total of 901 early-stage non-small cell lung cancer patients who underwent surgical treatment at Shanghai Chest Hospital between November 2015 and March 2017 were retrospectively included and randomly assigned to a training set (n=814) or testing set 1 (n=87). We subsequently included 116 patients who underwent surgical treatment and intraoperative frozen section between April 2019 and January 2020 to form testing set 2. We compared the performance of our deep learning approach in predicting tumor invasiveness with that of intraoperative frozen section analysis and human experts (radiologists and surgeons).ResultsThe deep learning approach yielded an area under the receiver operating characteristic curve (AUC) of 0.946 for distinguishing preinvasive adenocarcinoma from invasive lung adenocarcinoma in the testing set 1, which is significantly higher than the AUCs of human experts (P0.05) and junior thoracic surgeons (0.768, P>0.05).ConclusionsWe developed a deep learning model that achieved comparable performance to intraoperative frozen section analysis in determining tumor invasiveness. The proposed method may contribute to clinical decisions related to the extent of surgical resection.

BackgroundThis study aimed to examine the influence of serum inflammatory marker levels on long-term outcomes after liver resection in patients with intrahepatic cholangiocarcinoma (ICC).MethodsData from 1189 consecutive ICC patients who underwent liver resection were reviewed. The serum neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and prognostic nutritional index (PNI) were measured before surgery. Overall survival (OS) and tumour recurrence were analysed using the Kaplan–Meier method and compared using the log-rank test. Independent risk factors for OS and tumour recurrence were analysed using the Cox hazard regression model.ResultsWe identified elevated serum NLR (≥ 2.15) as an independent risk factor for both OS and tumour recurrence (hazard ratio [HR]: 1.327, 95% confidence interval [CI]: 1.105-1.593; HR: 1.274, 95% CI: 1.074-1.510) among the three inflammatory markers assessed. Elevated NLR was associated with higher carbohydrate antigen 19-9 (CA19-9) and carcinoembryonic antigen (CEA) levels, larger tumour size, multiple tumours, lymph node metastasis, vascular invasion, and more advanced tumour node metastasis (TNM) stage (III/IV). Subgroup analysis showed that elevated NLR was an independent risk factor for OS and tumour recurrence in patients with hepatitis B virus (HBV) infection compared with patients without HBV infection (HR: 1.347, 95% CI: 1.073-1.690; HR: 1.386, 95% CI: 1.112-1.726).ConclusionsElevated serum NLR was associated with worse prognosis among ICC patients who underwent liver resection, especially in patients with HBV infection.

ObjectivesTo explore whether the preoperative CT radiomics can predict the status of microsatellite instability (MSI) in colorectal cancer (CRC) patients and identify the region with the most stable and high-efficiency radiomics features.MethodsThis retrospective study involved 230 CRC patients with preoperative computed tomography scans and available MSI status between December 2019 and October 2021. Image segmentation and radiomic feature extraction were performed as follows. First, slices with the maximum tumor area (region of interest, ROI) were manually contoured. Subsequently, each ROI was shrunk inward by 1, 2, and 3 mm, respectively, where the remaining ROIs were considered as the internal region of the tumor (named as IROI1, IROI2, and IROI3), and the shrunk regions were considered as marginal regions of the tumor (named as MROI1, MROI2, and MROI3). Finally, radiomics features were extracted from each of the ROI. The intraclass correlation coefficient and least absolute shrinkage and selection operator method were used to choose the most reliable and relevant features of MSI status. Clinical, radiomics, and combined clinical radiomics models have been established. Calibration curve and decision curve analyses (DCA) were generated to explore the correction effect and assess the clinical applicability of the above models, respectively.ResultsIn the testing cohort, the radiomics model based on IROI3 yielded the highest average area under the curve (AUC) value of 0.908, compared with the remaining radiomics models. Additionally, hypertension and N stage were considered as clinically independent factors of MSI status. The combined clinical radiomics model achieved excellent diagnostic efficacy (AUC: 0.928; sensitivity: 0.840; specificity: 0.867) in the testing cohort, as well as favorable calibration and clinical utility by calibration curve and DCA analyses.ConclusionsThe IROI3 model, which is based on a 3-mm shrink in the largest areas of the tumor, could noninvasively reflect the heterogeneity and genetic instability within the tumor. This suggests that it is an important biomarker for the preoperative prediction of MSI status. The model can extract more robust and effective radiomics features, which lays a foundation for the radiomics study of hollow organs, such as in CRC.

BackgroundThe GALAD and ASAP scores are two well-recognized algorithms to estimate the risk of hepatocellular carcinoma (HCC) based on gender, age, alpha-fetoprotein (AFP), protein induced by vitamin K absence or Antagonist-II (PIVKA-II) and AFP-L3 (included in the GALAD score but not in the ASAP score). The current study sought to compare the diagnostic performance of each score to detect HCC among patients infected with hepatitis C virus (HCV).MethodsA multicenter case-control study was undertaken in which blood samples were collected from HCVinfected patients with and without HCC. Using the area under the receiver operating characteristic curve (AUROC), ASAP and GALAD scores were compared relative to diagnostic performance to detect any stage HCV-HCC and early-stage HCV-HCC.ResultsThe analytic cohort included 168 HCV-HCC patients and a control group of 193 HCV-infected patients. The ASAP score had a higher AUROC to detect any stage HCV-HCC versus the GALAD score, both in the overall group (0.917 vs. 0.894, P=0.057) and in the cirrhosis subgroup (0.909 vs. 0.889, P=0.132). Similar results were noted relative to the detection of early-stage HCV-HCC, whether defined by BCLC staging (stage 0-A: 0.898 vs. 0.860, P=0.026) or 8th TNM staging (stage I: 0.899 vs. 0.870, P=0.070). In subgroup analysis to detect AFP-negative HCV-HCC, the ASAP score also demonstrated a higher AUROC than the GALAD score to detect any stage HCV-HCC in the AFP-negative subgroup (0.815 vs. 0.764, P=0.063).ConclusionsThe ASAP score had better diagnostic performance for early detection of HCV-HCC compared with the GALAD score. The ASAP score may be preferrable to the GALAD score for HCC screening and surveillance among HCV-infected patients.

Yuying Chen,1,&ast; Jia Chen,2,&ast; Yu Zhang,3,&ast; Zhi Lin,1 Meng Wang,1 Lifei Huang,2 Mengqi Huang,1 Mimi Tang,1 Xiaoqi Zhou,1 Zhenpeng Peng,1 Bingsheng Huang,2 Shi-Ting Feng1 1Department of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of China; 2Medical AI Lab, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, Guangdong, People’s Republic of China; 3Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bingsheng HuangMedical AI Lab, School of Biomedical Engineering, Health Science Center, Shenzhen University, Shenzhen, Guangdong, People’s Republic of ChinaTel +86 755-86172208Fax +86 755-86171820Email huangb@szu.edu.cnShi-Ting FengDepartment of Radiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, People’s Republic of ChinaTel +86 20-87755766 Ext 8471Fax +86 20-87615805Email fengsht@mail.sysu.edu.cnPurpose: Cytokeratin 19 (CK19) expression is a proven independent prognostic predictor of hepatocellular carcinoma (HCC). This study aimed to develop and validate the performance of a deep learning radiomics (DLR) model for CK19 identification in HCC based on preoperative gadoxetic acid-enhanced magnetic resonance imaging (MRI).Patients and Methods: A total of 141 surgically confirmed HCCs with preoperative gadoxetic acid-enhanced MRI from two institutions were included. Prediction models were established based on hepatobiliary phase (HBP) images using a training set (n=102) and validated using time-independent (n=19) and external (n=20) test sets. A receiver operating characteristic curve was used to evaluate the performance for CK19 prediction. Recurrence-free survival (RFS) was also analyzed by incorporating the CK19 expression and other factors.Results: For predicting CK19 expression, the area under the curve (AUC) of the DLR model was 0.820 (95% confidence interval [CI]: 0.732– 0.907, P< 0.001) with sensitivity, specificity, accuracy of 0.800, 0.766, and 0.775, respectively, and reached 0.781 in the external test set. Combined with alpha fetoprotein, the AUC increased to 0.833 (95% CI: 0.753– 0.912, P

Despite the rapid advances in the liver-on-a-chip platforms, it remains a daunting challenge to construct a biomimetic liver-on-a-chip for in vitro research. This study aimed to reconstruct the tissue-tissue interfaces based on bilayer microspheres and form vascularized liver tissue. Firstly, we designed a tri-vascular liver-on-a-chip (TVLOC) comprising a hepatic artery, a portal vein and a central vein, and theoretically analyzed the distribution of velocity and concentration fields in the culture area. Secondly, we designed a bilayer microsphere generating microsystem based on the coaxial confocal principle, which is primarily used to produce bilayer microspheres containing different kinds of cells. Finally, the bilayer microspheres were co-cultured with endothelial cells in the cell culture area of the TVLOC to form vascularized liver tissue, and the cell viability and vascular network growth were analyzed. The results revealed that the TVLOC designed in this study can provide a substance concentration gradient similar to that of the liver microenvironment, and the bilayer microspheres can form a three-dimensional (3D) orderly liver structure with endothelial cells. Such a liver-on-a-chip is capable of maintaining the function of hepatocytes (HCs) pretty well. This work provides full insights into further simulation of the liver-on-a-chip.

ObjectiveThis study aimed to study the diagnostic efficacy of positron emission tomography (PET)/magnetic resonance imaging (MRI), computed tomography (CT) and clinical metabolic parameters in predicting the histological classification of lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC).MethodsPET/MRI, CT and clinical metabolic data of 80 patients with lung ADC or SCC were retrospectively collected. According to the pathological results from surgery or fiberscopy, the patients were diagnosed with lung ADC (47 cases) or SCC (33 cases). All 80 patients were divided into a training group (64 cases), an internal testing group (8 cases) and an external testing group (8 cases) in the ratio of 8:1:1. Nine models were constructed by integrating features from different modalities. The Gaussian classifier was used to differentiate ADC and SCC. The prediction ability was evaluated using the receiver operating characteristic curve. The area under the curve (AUC) of the models was compared using Delong’s test. Based on the best composite model, a nomogram was established and evaluated with a calibration curve, decision curve and clinical impact curve.ResultsThe composite model (PET/MRI + CT + Clinical) owned the highest AUC values in the training, internal testing and external testing sets, respectively. In the training set, significant differences in the AUC were found between the composite model and other models except for the PET/MRI + CT model. The calibration curves showed good consistency between the predicted output and actual disease. The decision curve analysis and clinical impact curves demonstrated that the composite model increased the clinical net benefit for predicting lung cancer subtypes.ConclusionThe composite prediction model of PET/MRI + CT + Clinical better distinguished ADC from SCC pathological subtypes preoperatively and achieved clinical benefits, thus providing an accurate clinical diagnosis.

Abstract Background Hepatectomy is an effective treatment for synchronous colorectal liver metastases (SCLM) patients. However, whether to choose simultaneous hepatectomy (SIH) or staged hepatectomy (STH) is still controversial, especially during major hepatectomy (≥3 liver segments). Aims Compare the difference between the SCLM patients underwent SIH and STH, especially during major hepatectomy (≥3 liver segments). Methods and Results A meta‐analysis was conducted by analyzing the published data on the outcomes of SCLM patients underwent SIH or STH from January 2010 to December 2020 from the electronic databases. A random‐effects model was used to derive pooled estimates of odds ratio (OR) with 95% confidence interval (CI) for the explored outcomes. Eventually, 18 studies, including 5101 patients, were included this study. The result of meta‐analysis showed that SIH did not increase postoperative complications (pooled OR: 1.037; 95% CI: 0.897–1.200), perioperative mortality (pooled OR: 0.942; 95% CI: 0.552–1.607), 3‐year mortality (pooled OR: 1.090; 95% CI: 0.903–1.316) or 5‐year mortality (pooled OR: 1.077; 95% CI: 0.926–1.253), as compared with STH. Subgroup analysis showed that, simultaneous major hepatectomy (SIMH) also did not increase postoperative complications (pooled OR: 0.863; 95% CI: 0.627–1.188) or perioperative mortality (pooled OR: 0.689; 95% CI: 0.290–1.637) as compared with staged major hepatectomy (STMH). Conclusion Postoperative complications, perioperative mortality and long‐term prognosis had no significant difference between SIH and STH for SCLM patients. Besides, postoperative complications and perioperative mortality also had no significant difference between SIMH and STMH.

PurposeThe aim of this study is to compare the blood oxygen level–dependent (BOLD) fluctuation power in 96 frequency points ranging from 0 to 0.25 Hz between benign and malignant musculoskeletal (MSK) tumors via power spectrum analyses using functional magnetic resonance imaging (fMRI).Materials and methodsBOLD-fMRI and T1-weighted imaging (T1WI) of 92 patients with benign or malignant MSK tumors were acquired by 1.5-T magnetic resonance scanner. For each patient, the tumor-related BOLD time series were extracted, and then, the power spectrum of BOLD time series was calculated and was then divided into 96 frequency points. A two-sample t-test was used to assess whether there was a significant difference in the powers (the “power” is the square of the BOLD fluctuation amplitude with arbitrary unit) of each frequency point between benign and malignant MSK tumors. The receiver operator characteristic (ROC) analysis was used to assess the diagnostic capability of distinguishing between benign and malignant MSK tumors.ResultsThe result of the two-sample t-test showed that there was significant difference in the power between benign and malignant MSK tumor at frequency points of 58 (0.1508 Hz, P = 0.036), 59 (0.1534 Hz, P = 0.032), and 95 (0.247 Hz, P = 0.014), respectively. The ROC analysis of mean power of three frequency points showed that the area of under curve is 0.706 (P = 0.009), and the cutoff value is 0.73130. If the power of the tumor greater than or equal to 0.73130 is considered the possibility of benign tumor, then the diagnostic sensitivity and specificity values are 83% and 59%, respectively. The post hoc analysis showed that the merged power of 0.1508 and 0.1534 Hz in benign MSK tumors was significantly higher than that in malignant ones (P = 0.014). The ROC analysis showed that, if the benign MSK tumor was diagnosed with the power greater than or equal to the cutoff value of 1.41241, then the sensitivity and specificity were 67% and 68%, respectively.ConclusionThe mean power of three frequency points at 0.1508, 0.1534, and 0.247 Hz may potentially be a biomarker to differentiate benign from malignant MSK tumors. By combining the power of 0.1508 and 0.1534 Hz, we could better detect the difference between benign and malignant MSK tumors with higher specificity.